Adiporedoxin suppresses endothelial activation via inhibiting MAPK and NF-kappa B signaling

作者：He, Hui; Guo, Fang; Li, Yong; Saaoud, Fatma; Kimmis, Brooks D.; Sandhu, Jeena; Fan, Michelle; Maulik, Dev; Lessner, Susan; Papasian, Christopher J.; Fan, Daping; Jiang, Zhisheng^*; Fu, Mingui^*

来源：Scientific Reports, 2016, 6(1): 38975.

DOI：10.1038/srep38975

• ENDOPLASMIC-RETICULUM STRESS
• CORONARY-ARTERY-DISEASE
• HYDROGEN-PEROXIDE
• ATHEROSCLEROSIS
• INFLAMMATION
• DYSFUNCTION

Adiporedoxin (Adrx) is a recently discovered redox regulatory protein that is preferentially expressed in adipose tissue and plays a critical role in the regulation of metabolism via its modulation of adipocyte protein secretion. We here report that Adrx suppresses endothelial cell activation via inhibiting MAPK and NF-kappa B signaling pathways. Adrx is constitutively expressed in human vascular endothelial cells, and significantly induced by a variety of stimuli such as TNF alpha, IL-1 beta, H2O2 and OxLDL. Overexpression of Adrx significantly attenuated TNF alpha-induced expression of VCAM-1 and ICAM-1, and thus reduced monocyte adherence to human umbilical vein endothelial cells (HUVECs). Conversely, siRNA-mediated knockdown of Adrx increased TNF alpha-induced expression of adhesion molecules and monocyte adherence to HUVECs. Furthermore, forced expression of Adrx decreased TNF alpha-induced activation of ERK1/2, JNK, p38 and IKKs in HUVECs. Adrx mutant in the CXXC motif that lost its anti-redox activity is less efficient than the wild-type Adrx, suggesting that Adrx-mediated inhibition of endothelial activation is partially dependent on its antioxidant activity. Finally, Adrx expression was markedly increased in human atheroma compared with normal tissue from the same carotid arteries. These results suggest that Adrx is an endogenous inhibitor of endothelial activation, and might be a therapeutic target for vascular inflammatory diseases.

• 出版日期2016-12-12
• 单位南昌大学; 南华大学